Therapeutic potential of varenicline in neuropsychiatric disorders: insights into its molecular mechanisms.

Neuropsychiatric disorders pose significant health challenges. Current drug therapies are often inadequate, highlighting the urgent need for new and effective treatments. The α4β2 nicotinic receptor has been implicated in the pathophysiology of various neuropsychiatric disorders. In this context, varenicline, its selective agonist, has garnered increasing attention for its potential therapeutic effects across a range of neuropsychiatric conditions. Emerging preclinical evidence suggests that varenicline may exert neuroprotective effects through modulation of pathways that include synaptic plasticity and synaptic proteins, neuroinflammation, microglial activation, apoptosis, and autophagy. However, direct target engagement for many of these pathways has not yet been established. In this review, we provide a comprehensive review of the cellular and molecular mechanisms by which varenicline might be expected to exert therapeutic effects in a range of neuropsychiatric disorders. Most previous reviews of varenicline have concentrated on its use as a smoking cessation aid or on its potential to treat individual diseases. The current review takes a different approach, focusing at the molecular level on the various pathways that are affected in different diseases, and discussing within each section the evidence that currently exists in relation to each of these in studies conducted in rodent models and in clinical trials. The review seeks to provide insight into the potential benefits and drawbacks of using a single compound to treat a variety of disorders, and to highlight areas for future research.